Ventricular Outflow Tract Obstruction Research Articles

Left ventricular posterior wall hypertrophy leads to poor prognosis of hypertrophic obstructive cardiomyopathy in children - a cohort study.

The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, we aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional(3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis. We retrospectively analyzed 57 children with HOCM from April 2015 to October 2022, among whom 16 underwent preoperative CCT examination. All children underwent the modified Morrow surgery in our center. We defined heart failure (HF), malignant ventricular arrhythmia, and recurrent left ventricular outflow tract obstruction (LVOTO) as adverse events. We performed a retrospective Cox analysis and conducted genetic testing. A 3D model of the LV was built through the standard 17-segment method and analyzing the high-risk factors. 17 (29.8%) had adverse events during follow-up. Multivariate Cox analysis revealed that genetic mutation (HR:5.634, 95%CI:1.663-19.086, P=0.005), Noonan syndrome (HR:3.770, 95%CI:1.245-11.419, P=0.019), preoperational systolic anterior motion (SAM)(HR:4.596, 95%CI:1.532-13.792, P=0.007)and mid-ventricular obstruction (HR:4.763, 95%CI:1.538-14.754, P=0.007) were high-risk factors, suggesting that the degree of hypertrophy in the left ventricle is associated with poor prognosis. By analyzing the CCT with 3D model, children with poor prognosis have more hypertrophy in basal-inferior (P=0.014), mid-inferoseptal(P=0.044), mid-inferior(P=0.017). It suggests that a more hypertrophied posterior left ventricular wall portends a worse prognosis. Even after modified Morrow surgery, the prognostic impact of genetic mutation remains significant. Moreover, the degree of hypertrophy of the posterior wall in the LV was also related to the postoperative prognosis through CCT combined with 3D technology. It provides surgeons guiding to evaluate the overall prognosis and the treatment plan before surgery.

Percutaneous coronary intervention in patients with hypertrophic cardiomyopathy and coronary artery disease

Background Coronary artery disease and left ventricular outflow tract obstruction may overlap in symptoms in patients with hypertrophic cardiomyopathy. It has not been clear if coronary revascularization relieves exertional symptoms in patients with hypertrophic cardiomyopathy. Methods We reviewed 156 patients with hypertrophic cardiomyopathy who underwent percutaneous coronary intervention at Anzhen Hospital from 2009 to 2019. Improvement in symptoms after the percutaneous coronary intervention was investigated. Results The mean age was 60.8 ± 9.8 years, and 116 (74.4%) were men. The main symptoms of the patients were chest tightness in 115 (73.7%), chest pain in 88 (56.4%), dyspnea in 50 (32.1%), palpitation in 22 (14.1%), and presyncope/syncope in 12 (7.7%). At rest, the systolic anterior motion of the mitral valve was observed in only 36 patients. Among the 156 patients, 64 had single-vessel disease, 46 had two-vessel diseases, and the other 46 had three-vessel diseases. There was no early mortality in the present cohort. After the coronary intervention, there were significant improvements in symptoms including chest tightness (6.4%), chest pain (1.3%), dyspnea (2.6%), and palpitation (8.3%). In 93 patients with follow-up data, the overall survival was 77% at 10 years and the survival free from intervention was 60% at 10 years. Conclusions In patients with hypertrophic cardiomyopathy, coronary artery disease can be an important cause of symptoms and should be screened. Percutaneous coronary intervention is safe and effective for coronary revascularization. Cardiac symptoms can be significantly relieved and long-term outcomes are favorable.

Midterm Outcomes: A Comprehensive Approach to Surgery for Hypertrophic Obstructive Cardiomyopathy

BackgroundLeft ventricular outflow tract (LVOT) obstruction in obstructive hypertrophic cardiomyopathy (HCM) is caused by a constellation of abnormalities. This study reviewed outcomes of a comprehensive approach to correct these abnormalities during surgery. MethodsThis was a single-institution study of patients with HCM who underwent septal myectomy from 2016 to 2023. Their New York Heart Association functional classification and most recent echocardiogram that estimated LVOT gradient and mitral valve function were tracked. ResultsThe study included 103 patients with a mean age of 54 years (interquartile range, 40-67 years) and common comorbidities: hypertension (50%) and atrial fibrillation (25%). On average, the preprocedure resting echocardiogram showed an LVOT gradient of 36.4 mm Hg and moderate or severe mitral regurgitation in 50.5% of patients. All patients underwent septal myectomy, and associated abnormalities contributing to LVOT obstruction were addressed. Elongation of the anterior leaflet of the mitral valve was typically treated with papillary muscle realignment (72%). Aberrant papillary muscle heads and elongated secondary chordae tendineae contributing to systolic anterior motion were resected (66%). Myocardial bands, including apicoseptal bands contributing to LVOT obstruction, were resected (68%). With an average follow-up of 4 years, 91% of patients were considered to be in New York Heart Association functional class I or II. Long-term echocardiographic follow-up showed a mean peak LVOT gradient of 11 mm Hg (interquartile range, 4-13 mm Hg). Only 1 patient had more than mild mitral regurgitation. ConclusionsA comprehensive surgical approach to HCM that addresses the entire constellation of abnormalities associated with HCM, including mitral valve anterior leaflet elongation, aberrant or displaced mitral valve subvalvular apparatus, and myocardial bands, leads to outstanding midterm outcomes.

An overview of the treatments for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a very prevalent inherited disease with a wide global distribution and a prevalence rate of approximately 0.2% in the general population. Left ventricular hypertrophy (LVH) caused by sarcomere mutation is the primary reason of HCM. The histopathology feature is that cardiomyocyte hypertrophy, myocyte disorder and myocardial fibrosis lead to diminished diastolic function, left ventricular outflow tract obstruction (LVOTO) and arrhythmia, all of which result in serious cardiac complications. Previously, HCM was considered a malignant disease that was almost untreatable. With the improvement of medical standards and increasing awareness of HCM, it has become a highly treatable disease in contemporary times, with a significant decrease in mortality rates. However, there are still significant unmet requirements in the therapy of HCM. This paper draws on more than 100 references from the past four decades and summarizes current advances in the treatment of HCM. The article will review the pathogenesis and types, recent development in pharmacotherapy, invasive treatments and gene therapies, as well as dilemma and future development of HCM.

The Role of Alcohol Ablation Therapy in Hypertrophic Obstructive Cardiomyopathy Management

Objectives: The following study aims to investigate alcohol septal ablation’s (ASA) role in hypertrophic obstructive cardiomyopathy (HOCM) management, focusing on in-hospital outcomes, efficacy in reducing left ventricular outflow tract (LVOT) obstruction, and safety profiles. Methods: The study, conducted at the Institute of Cardiology, National Hospital of Sri Lanka, included a total of nine HOCM patients. Participants with exercise-induced symptoms, dyspnea/angina, and specific ventricular gradients were included; unidentified septal branches led to exclusion. Diagnostic assessments, including electrocardiogram, contrast echocardiography, and cardiac catheterization, confirmed HOCM. ASA procedures involved careful target septal branch selection, alcohol injection, and post-procedure care with temporary pacemaker monitoring. Results: The study population (N=9) comprised seven males and two females, with a mean age of 40. Pre- and post-ablation measurements showed 78% reduction in LVOT gradient. Immediate complications included chest pain (100%), while 22.2% developed complete heart block. Notably, no mortality occurred during the study. Conclusion: ASA proved safe and effective in managing HOCM, with significant mean reduction in post-ablation LVOT gradient (78%). Complications were generally minor, emphasizing ASA’s viability for symptomatic HOCM patients. While acknowledging the absence of randomized controlled trials comparing ASA with alternative techniques, this study contributes valuable insights to guide collaborative treatment decisions by specialists.

Changes in left ventricular-aortic angulation are associated with the development of obstruction in hypertrophic cardiomyopathy

ObjectiveTo characterize changes in ventricular morphology in patients with hypertrophic cardiomyopathy who develop left ventricular (LV) outflow tract obstruction. MethodsWe reviewed patients with hypertrophic cardiomyopathy with LV outflow tract obstruction who underwent septal myectomy from May 2012 to June 2023. Among 68 patients initially without obstruction documented up to 7.6 years (interquartile range, 6.3-9.4 years) before the operation, a comparison was made with 78 patients with nonobstructive hypertrophic cardiomyopathy over a similar period. Patients who did not develop obstruction were matched with those who did on sex, age, and maximum septal wall thickness during the initial echocardiography, identifying 41 matched pairs. Echocardiographic data, including 5 measures of angulation, were compared between the groups. ResultsThe median interval between echocardiographic assessments was 7.5 years (interquartile range, 6.3-8.1 years) among patients with obstruction versus 7.3 years (interquartile range, 6.2-9.0 years) in patients without nonobstruction. Patients with obstruction were more likely to have hypertension at both times. The maximum septal wall thickness increased within both groups (both P values < .001), but the magnitude of increase was not different between groups (P = .130). Patients with obstruction exhibited a greater increase in LV mass (P < .001) compared with patients without obstruction (P = .004). Aortic angulation significantly increased in 4 of the 5 measurements (all P values < .001) in patients with obstruction, whereas patients with no obstruction showed no change. Anterior and posterior mitral valve leaflet lengths and coaptation lengths remained similar in both groups over time. ConclusionsThe development of LV outflow tract obstruction in patients with hypertrophic cardiomyopathy was associated with progressive LV outflow tract angulation and increased LV hypertrophy, as reflected by LV mass. Progression to obstruction was not related to changes in the mitral valve leaflet morphology.

Genetic variations in PTPN11 lead to a recurrent Left Ventricular Outflow Tract Obstruction phenotype in childhood hypertrophic cardiomyopathy

ObjectiveLeft ventricular septal myotomy provides a favorable prognosis for children with hypertrophic obstructive cardiomyopathy (HOCM). However, some children still suffer from recurrent left ventricular outflow tract obstruction (LVOTO) after surgery. Poor prognosis exists for HOCM caused by PTPN11 mutation. Therefore, the aim of this study was to determine the clinical features of recurrent obstruction in children with HOCM caused by pathogenic mutations in the PTPN11 gene. MethodsA total of 56 children were diagnosed with HOCM underwent septal myectomies. Whole exome sequencing of 49 pediatric cardiomyopathies associated genes (including PTPN11) were performed. We performed hematoxylin-eosin(H&E), Masson, and wheat germ agglutinin (WGA)staining of tissues positive for PTPN11 and those negative for PTPN11 were conducted. ResultsWhole exome sequencing results showed 11 PTPN11 mutation (19.6%) children. In long-term follow-up (median 37 months, maximum 9 years), children with PTPN11 mutation had 6(54.5%) recurrent LVOTO compared with other groups (P=.015), but similar survival rates(P=.514). The mean postoperative time to recurrent obstruction was 22±27 months. Children with PTPN11 mutation were 9-fold more likely to experience the risk associated with recurrent obstruction (95% CI = 1.77-45.81, P<.001). H&E, Masson and WGA staining also revealed more cardiomyocyte hypertrophy in PTPN11 mutation tissues. See Figure 4 for a graphical abstract of the study. ConclusionChildren with PTPN11 mutation-associated hypertrophic cardiomyopathy have a higher risk of recurrent LVOTO.

Prevention of SAM phenomenon after reconstructive mitral valve surgery

Systolic anterior motion (SAM) of the mitral valve (MV) can be a life-threatening condition. The SAM can result in severe left ventricular outflow tract obstruction and/or mitral regurgitation and is associated with up to 20% risk of sudden death (which is substantially lower in hypertrophic cardiomyopathy (HCM)).The mechanisms of SAM are complex and depend on the functional status of the ventricle. The SAM can occur in all cases, but is typically observed in patients with HCM or following MV repair.Echocardiography (2D, 3D and stress) has a central diagnostic role as the application of echocardiographic SAM predictors allows the incorporation of prevention techniques during surgery and post-operative SAM assessment.MRI (magnetic resonance imaging) has a special role in understanding the dynamic nature of SAM, especially in anatomically atypical hearts (including HCM).This article describes what the clinician needs to know about SAM ranging from pathophysiological mechanisms and imaging modalities to conservative (medical) and surgical approaches and their respective outcomes.A stepwise approach consisting of medical therapy, followed by aggressive volume loading and beta-adrenoreceptor blockers. Surgery is the final option. The correct choice of surgical technique requires an understanding of the anatomical substrate of SAM.

Unmasking Obstruction in Hypertrophic Cardiomyopathy With Postprandial Resting and Treadmill Stress Echocardiography

Latent left ventricular outflow tract obstruction (LVOTO) is an important cause of symptoms in patients with hypertrophic cardiomyopathy (HCM) but can be challenging to provoke. To examine the value of postprandial resting and stress echocardiography and utilization of invasive or enhanced drug therapies (surgical myectomy, alcohol septal ablation, disopyramide, and mavacamten) in patients with postprandial LVOTO. Consecutive HCM patients without LVOTO underwent routine and postprandial echocardiography at rest, with provocation (Valsalva and standing) and after symptom-limited treadmill stress. Among 252 patients (mean age, 58years, 39% women), postprandial LVOT gradients were higher compared with routine echocardiography at rest (median, 9.0 [0-38.0] vs 0 [0-14.0] mm Hg; P<.0001) and with provocation (18.5 [0-70.3] vs 1.5 [0-41.0] mm Hg; P<.0001). Postprandial exercise stress echocardiogram (PPXSE) gradients were higher in a subset of 44 patients who underwent both postprandial and fasting stress echocardiography (47.0 [5.3-81.0] vs 17.5 [0-46.0] mm Hg; P<.0001). In total, 49 (19.5%) patients achieved the ≥50mm Hg threshold under routine conditions (rest/provocation); 90 (35.7%) additional patients achieved postprandial gradients ≥50mm Hg (rest/provocation/exercise), 38 (15.1%) with PPXSE alone. A total of 71 patients were treated with 91 invasive or enhanced drug therapies, 32 (45.1%) of whom had gradients ≥50mm Hg only after eating (rest/provocation) and 8 (11.3%) only with PPXSE, with symptom relief in the majority. Postprandial echocardiography was useful at unmasking LVOTO in more than one-third of patients who did not have high gradients otherwise. Eating before echocardiography is a powerful provocative tool in the evaluation of patients with HCM.

Association of left ventricular outflow tract size with arch morphology in interrupted aortic arch.

Left ventricular outflow tract obstruction (LVOTO) is a major cause of morbidity and mortality in infants with interrupted aortic arch (IAA). LVOT development may be flow-mediated, thus IAA morphology may influence LVOT diameter and subsequent reintervention. We investigated the association of IAA morphology (type and presence of aortic arch aberrancy) with LVOT diameter and reintervention. All surgical patients with IAA (2001-2022) were reviewed at a single institution. We compared IAA-A versus IAA-B; IAA with aortic arch aberrancy (AAb) versus none; IAA-B with aberrant subclavian artery (AAbS) versus Others. Primary outcomes included LVOT diameter (mm), LVOTO at discharge (≥50mmHg), and LVOT reintervention. Seventy-seven infants (mean age 10±19 days) were followed for 7.6 (5.5-9.7) years. Perioperative mortality was 3.9% (3/77) and long-term mortality was 5.2% (4/77). Out of 51 IAA-B (66%) and 22 IAA-A (31%) patients, 30% (n = 22) had AAb. Smaller LVOT diameter was associated with IAA-B [IAA-A: 5.40 (4.68-5.80), IAA-B: 4.60 (3.92-5.50), p = 0.007], AAb [AAb: 4.00 (3.70-5.04) vs None: 5.15 (4.30-5.68) p = 0.006], and combined IAA-B+AAbS [IAA-B+AAbS: 4.00 (3.70-5.02) vs Other: 5.00 (4.30-5.68), p = 0.002]. The likelihood of LVOTO was higher among AAb (N = 6 (25%) vs N = 1 (2%), p = 0.004) and IAA-B+AAbS (N = 1 (2%) vs N = 6 (30%), p = 0.002). Time-to-event analysis showed a signal towards increased LVOT reintervention in IAA-B+AAbS (p = 0.11). IAA-B and AAb are associated with small LVOT diameter and early LVOTO, especially in combination. This may reflect lower flow in the proximal arch during development. Most reinterventions occur in IAA-B+AAbS, hence these patients should be carefully considered for LVOT intervention at the time of initial repair.

Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: do mitral valve leaflet length, septal thickness, or sex affect the outcome?

This retrospective cohort study aimed to assess whether basal septal wall thickness (BSWT), anterior (AML) and posterior (PML) mitral leaflet length, or sex were associated with remaining left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA). One hundred fifty-four patients who underwent ASA at the Karolinska University Hospital in Stockholm, Sweden, between 2009 and 2021, were included retrospectively. Anatomical and hemodynamic parameters were collected from invasive catheterization before and during ASA, and from echocardiography (ECHO) examinations before, during, and at 1-year follow-up after ASA. Linear and logistic regression models were used to assess the association between sex, BSWT, AML, PML, and outcome, which was defined as the remaining LVOTO (≥ 30 mmHg) after ASA. The median follow-up was 364 days (interquartile range 334–385 days). BSWT ≥ 23 mm (n = 13, 12%) was associated with remaining LVOTO at follow-up (p = 0.004). Elongated mitral valve leaflet length (either AML or PML) was present in 125 (90%) patients. Elongated AML (> 24 mm) was present in 67 (44%) patients, although AML length was not associated with remaining LVOTO at follow-up. Elongated PML (> 14 mm) was present in 114 (74%) patients and was not associated with remaining LVOTO at follow-up. No significant sex differences were observed regarding the remaining LVOTO. ECHO measurement of BSWT can be effectively used to select patients for successful ASA and identify those patients with a risk of incomplete resolution of LVOTO after ASA.Graphical abstract

Role of Transesophageal Echocardiography in Differentiating Dynamic versus Fixed Left Ventricular Outflow Tract Obstruction in Complete Transposition of Great Arteries: A Rare Case Report

Role of Transesophageal Echocardiography in Differentiating Dynamic versus Fixed Left Ventricular Outflow Tract Obstruction in Complete Transposition of Great Arteries: A Rare Case Report

Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

Characteristics and outcomes associated with sarcomere mutations in patients with hypertrophic cardiomyopathy: A systematic review and meta-analysis

BackgroundHypertrophic cardiomyopathy (HCM) is an inherited heart disease that can lead to sudden cardiac death. Impact of genetic testing for the prognosis and treatment of patients with HCM needs to be improved. We conducted a systematic review and meta-analysis to investigate the characteristics and outcomes associated with sarcomere genotypes in index patients with HCM. MethodsA systematic search was conducted in Medline, Embase, and Cochrane Library up to Dec 31, 2023. Data on clinical characteristics, morphological and imaging features, outcomes and interventions were collected from published studies and pooled using a random-effects meta-analysis. ResultsA total of 30 studies with 10,825 HCM index patients were included in the pooled analyses. The frequency of sarcomere genes in HCM patients was 41%. Sarcomere mutations were more frequent in women (p < 0.00001), and were associated with lower body mass index (26.1 ± 4.7 versus 27.5 ± 4.3; p = 0.003) and left ventricular ejection fraction (65.7% ± 10.1% vs. 67.1% ± 8.6%; p = 0.03), less apical hypertrophy (6.5% vs. 20.1%; p < 0.0001) and left ventricular outflow tract obstruction (29.1% vs. 33.2%; p = 0.03), greater left atrial volume index (43.6 ± 21.1 ml/m2 vs. 37.3 ± 13.0 ml/m2; p = 0.02). Higher risks of ventricular tachycardia (23.4% vs. 14.1%; p < 0.0001), syncope (18.3% vs. 10.9%; p = 0.01) and heart failure (17.3% vs. 14.6%; p = 0.002) were also associated with sarcomere mutations. ConclusionsSarcomere mutations are more frequent in women, and are associated with worse clinical characteristics and poor outcomes.

The CHOIR study: acute hemodynamic effects of different pacing strategies in hypertrophic obstructive cardiomyopathy

Abstract Background The majority of patients with hypertrophic cardiomyopathy present with dynamic left ventricular (LV) outflow tract obstruction (LVOTO), referred to as hypertrophic obstructive cardiomyopathy (HOCM). Symptomatic treatment aims at reducing LVOTO with either medical therapy, invasive septal reducing therapies, or pacemaker therapy. There is conflicting evidence regarding the efficacy of pacemaker therapy. The effect of pacing strategies at physical exertion has not been investigated in HOCM. Purpose To identify the optimal pacing strategy for reducing LVOTO without compromising cardiac output at rest and exercise in HOCM. Methods In this ongoing project, we have so far included eight patients with symptomatic HOCM referred to our hospital for alcohol septal ablation (ASA). The day before ASA, we placed temporary pacing leads in the right atrium, the right ventricular (RV) apex and on the LV lateral wall. We also inserted a pulmonary artery catheter and performed per operative echocardiography. All patients had sinus rhythm. Intrinsic rhythm served as baseline and was followed by atrial sensed RV pacing, LV pacing and biventricular (BiV) pacing at rest and during supine cycling. We assessed LVOTO by echocardiography, and cardiac output by the thermodilution method under intrinsic rhythm and all pacing modalities. Results The mean age was 52±15 years, and two of eight patients were female. The mean maximal LV wall thickness was 16±1 mm. The resting LVOTO was 50±23 mmHg. Due to difficulties in placing the LV lead within a reasonable time frame, complete study protocol was not performed in all patients. All eight patients performed RV pace at rest, but only five patients (63 %) were LV and BiV paced at rest. Five patients performed supine cycling but only four patients completed with RV and BiV pacing. The graphs display LVOTO and CO in sinus rhythm and the different pacing maneuvers at rest and during supine cycling. At rest, 6 out of 8 patients (75%) had LVOTO reduction during RV pace, and CO was unchanged. Four of five patients (80%) had LVOTO reduction during BiV and LV pace compared to sinus rhythm, also with unchanged CO. During supine cycling four of five patients (80%) had a reduction of the LVOTO gradient during RV and BiV pacing, without significant CO change. No complications occurred during the interventions. Conclusion In this ongoing study on cardiac pacing in HOCM, RV, LV, and BiV pacing reduced LVOTO while CO remained unchanged at rest and during exercise.

Genotype, phenotype and outcomes of patients with hypertrophic cardiomyopathy referred for ablation of ventricular tachycardia

Abstract Background Sustained monomorphic ventricular tachycardia (SMVT) is the most common ventricular arrhythmia (VA) subtype in patients with hypertrophic cardiomyopathy (HCM) who have received an implantable cardioverter defibrillator (ICD). However, data on catheter ablation (CA) are limited and available series typically report results of non-genotyped patients with relatively mild hypertrophy and/or apical aneurysms. Purpose This study describes genotype, phenotype and outcome of consecutive HCM patients referred for CA ablation of refractory SMVT. Methods and results Nine out of 787 patients referred for catheter ablation of SMVT between 01/2016 – 10/2023 had a HCM phenotype, 8/9 with dominant septal hypertrophy, none with LV outflow tract obstruction, and only 1/9 with an apical aneurysm. The median maximal wall thickness was 25 mm (IQR 20,2 – 26,9 mm) and the median left ventricular ejection fraction 34 % (IQR 26-42%). Six patients had a class IV/V variant in the myosine binding protein C (MYBPC3) gene, in 3 no disease-causing variant was identified. All patients with MYBPC3 mutation presented with an electrical storm/incessant VT refractory to antiarrhythmic drugs (AAD), including amiodarone (6/6) and amiodarone + class I AAD (3/6). In an attempt to control VT, 4/6 patients with a MYBPC3 variant required ≥2 ablation including bail out strategies (transcoronary alcohol-ablation, bipolar ablation, half-saline), surgical substrate resection and intraoperative cryoablation (3/6) and radiotherapy (2/6). After a median follow-up of 25 months (IQR 2-75) after the last intervention, all patients with MYBPC3-variants had VT recurrence, 3/6 died and 1/6 underwent heart transplantation. In contrast, patients without class IV/V variants, did not require bail-out strategies; VT recurred in one (single episode) and one patient died, 24 months after CA. The time course of the disease, management and outcome for patients with and without disease causing mutation is illustrated, with the first ablation as center line (figure). Conclusions Only 1 % of patients referred for CA of SMVT to a high-volume center had a HCM phenotype. A MYBPC3 variant was identified in 67%, and, in contrast to prior reports, 89% had severe hypertrophy. VT free survival appears to be particularly poor in MYBPC3 variant carriers despite availability of all treatment modalities. In these patients, early screening for advanced heart failure management including heart transplantation is important.

Phenotypic spectrum of the first Belgian MYBPC3 founder: a large multi-exon deletion with a varying phenotype.

Variants in the MYBPC3 gene are a frequent cause of hypertrophic cardiomyopathy (HCM) but display a large phenotypic heterogeneity. Founder mutations are often believed to be more benign as they prevailed despite potential negative selection pressure. We detected a pathogenic variant in MYBPC3 (del exon 23-26) in several probands. We aimed to assess the presence of a common haplotype and to describe the cardiac characteristics, disease severity and long-term outcome of mutation carriers. Probands with HCM caused by a pathogenic deletion of exon 23-26 of MYBPC3 were identified through genetic screening using a gene panel encompassing 59 genes associated with cardiomyopathies in a single genetic center in Belgium. Cascade screening of first-degree relatives was performed, and genotype positive relatives were further phenotyped. Clinical characteristics were collected from probands and relatives. Cardiac outcomes included death, heart transplantation, life-threatening arrhythmia, heart failure hospitalization or septal reduction therapy. Haplotype analysis, using microsatellite markers surrounding MYBPC3, was performed in all index patients to identify a common haplotype. The age of the founder variant was estimated based on the size of the shared haplotype using a linkage-disequilibrium based approach. We identified 24 probands with HCM harbouring the MYBPC3 exon 23-26 deletion. Probands were on average 51 ± 16years old at time of clinical HCM diagnosis and 62 ± 10 years old at time of genetic diagnosis. A common haplotype of 1.19Mb was identified in all 24 probands, with 19 of the probands sharing a 13.8Mb haplotype. The founder event was estimated to have happened five generations, or 175-200years ago, around the year 1830 in central Flanders. Through cascade screening, 59 first-degree relatives were genetically tested, of whom 37 (62.7%) were genotype positive (G+) and 22 (37.3%) genotype negative (G-). They were on average 38 ± 19years old at time of genetic testing. Subsequent clinical assessment revealed a HCM phenotype in 19 (51.4%) G+ relatives. Probands were older (63 ± 10 vs. 42 ± 21years; p < 0.001) and had more severe phenotypes than G+ family members, presenting with more symptoms (50% vs. 13.5%; p = 0.002), arrhythmia (41.7% vs. 12.9%, p = 0.014), more overt hypertrophy and left ventricular outflow tract obstruction (43.5% vs. 3.0%; p < 0.001). Male G+ relatives more often had a HCM phenotype (78.6% vs. 34.8%; p = 0.010) and were more severely affected than females. At the age of 50, a penetrance of 78.6% was observed, defined as the presence of HCM in 11 of 14 G+ relatives with age ≥50years. Overall, 20.3% of all variant carriers developed one of the predefined cardiac outcomes after a median follow-up of 5.5years with an average age of 50 (±21) years. A Belgian founder variant, an exon 23-26 deletion in MYBPC3, was identified in 24 probands and 37 family members. The variant is characterized by a high penetrance of 78.6% at the age of 50years but has variable phenotypic expression. Adverse outcomes were observed in 20.3% of patients during follow-up.

Natural history and clinical outcomes of patients with hypertrophic cardiomyopathy from thin filament mutations.

Hypertrophic cardiomyopathy (HCM) due to thick filament variants is more common; however, HCM due to thin filament variants (HCM-Thin) may be associated with a more malignant phenotype with an increased risk of sudden cardiac death. The aim of this study was to review all the published cases of HCM-Thin to better understand the natural history and clinical outcomes of this disease. A literature review of HCM-Thin identified 21 studies with a total of 177 patients that were suitable for analysis. There were three outcomes of interest, which included a heart failure composite, a ventricular arrhythmia composite and a heart failure and arrhythmia composite outcome. Kaplan-Meier (KM) survival analyses for freedom from each of the abovementioned composite outcomes were completed for the entire cohort and stratified by age of onset and sarcomeric variant. The heart failure composite occurred in 24 (13.6%) patients, the ventricular arrhythmia composite occurred in 30 patients (16.9%) and the combined heart failure and arrhythmia composite occurred in 50 patients (28.2%). In regard to left ventricular ejection fraction (LVEF), the majority of patients were preserved (LVEF>50%) compared with mildly reduced (LVEF 41%-50%) and reduced (LVEF≤40%) (respectively 26.6% vs. 0.6% vs. 3.4%). The median maximal left ventricular wall thickness (LVWT) was 19.0mm [interquartile range (IQR) 5.3]. Only 10.7% of the cohort had evidence of left ventricular outflow tract (LVOT) obstruction. Those with paediatric-onset HCM had earlier onset and were at higher risk for each endpoint than their adult counterparts. When stratified by genetic variant, patients with TNNI3 and TPM1 were at a higher risk of the heart failure composite endpoint and the combined heart failure and arrhythmia composite endpoint in comparison with those with the other genetic variants. HCM-Thin is associated with significant morbidity and mortality, with a high arrhythmia burden despite low rates of cardiac obstruction and mild hypertrophy. The paediatric onset of disease and certain sarcomeric variants appear to be associated with a worse prognosis than their adult-onset and other sarcomeric variant counterparts. HCM-Thin seems to have a distinct phenotype, which may require a different management approach.

A 20–YEAR FOLLOW–UP OF SUCCESSFUL SURGICAL MANAGEMENT OF DOUBLE–OUTLET RIGHT VENTRICLE WITH PULMONARY STENOSIS: A CASE REPORT

Abstract A 25–year–old man, suffering from worsening exertional dyspnea for 4 months, was referred to our Cardiology Unit. The patient was previously diagnosed with a late diagnosis of double outlet right ventricle (DORV), as well as pulmonary stenosis, VSD, and right–sided aortic arch for which he underwent a first surgical procedure around the age of 2 involving an intersternal anastomosis through a left lateral thoracotomy approach. A second intervention took place 2 years later for a radical correction of the anomaly through a median sternotomy. The patient had sporadic follow–up since then. A baseline ECG was performed, showing evidence of sinus rhythm, normal AV with a bifid P wave in lead II, slight RAD, incomplete RBBB, and asymmetric negative T waves from V1 to V3 and in aVL, and biphasic T waves in V4–V5. We performed an echocardiogram which showed: a dilated RA, a normal–sized LA, an apparently intact interatrial septum without evident shunts; a normal sized LV; EF 60%; a moderately dilated, hypertrophic and hypertrabeculated RV; FAC 33%; normal aortic flow; a minimal MR; a massive residual pulmonary insufficiency; a moderate TR; a dilatated pulmonary trunk; a normal–sized and collapsible IVC upon inspiration; PAPs of 70 mmHg; no pericardial effusion. A maximal exercise stress test appeared to be normal throughout. However, due to the severe pulmonary hypertension he was referred to our PH centre. While these patients are commonly affected by residual early or late left ventricular outflow tract obstruction, fortunately our patient was not. DORV is a relatively common congenital heart defect characterized by an abnormal connection between the ventricles and arteries, in which both the aorta and the pulmonary trunk are connected completely or predominantly to the right ventricle. The anatomical spectrum of this anomaly is quite large, and it can be associated with the presence of a VSD that often extends towards one or both of the arterial valves, allowing the flow of blood from the left ventricle to the aorta. An accurate diagnosis through echocardiography or CMR is essential in order to guide the surgical repair and the appropriate therapeutic approach for individuals affected by this anomaly. A successful surgical correction of DORV is essential, but it is important to be aware of the potential complications of post–operative PH (especially in patients with preoperative PH), which necessitates close surveillance and appropriate therapeutic management.

Computer-Assisted Transcatheter Mitral Valve Implantation for Valve-in-Valve Procedures.

Transcatheter mitral valve-in-valve is an alternative to high-risk reoperation on a failing bioprosthesis. It entails specific challenges such as left ventricular outflow tract obstruction. We propose a patient-specific augmented imaging based on preoperative planning to assist the procedure. Valve-in-valve simulation was performed to represent the optimal level of implantation and the neo-left ventricular outflow tract. These data were combined with intraoperative images through a real-time 3D/2D registration tool. All data were collected retrospectively on one case (pre and per-procedure imaging). We present for the first time an intraoperative guidance tool in transcatheter mitral valve-in-valve procedure.